Preparation and Fabrication Method of a Highly Repairing Composite Bio-based Leak-proof Patch
By preparing a composite biological leak-proof patch with a three-layer structure, the catechin functional groups of polyether ester catechins are used to achieve strong adhesion and bioactivity, which solves the problems of insufficient adhesion and limited bioactivity in the existing technology, and achieves the effects of immediate sealing and promoting tissue repair.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- SHANDONG MIANYITONG MEDICAL TECHNOLOGY CO LTD
- Filing Date
- 2026-05-26
- Publication Date
- 2026-06-30
Smart Images
Figure CN122297783A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of composite biological patch technology, specifically referring to the preparation and fabrication method of a strong repair composite biological leak-proof patch. Background Technology
[0002] Composite bio-leak-proof patch technology is attracting increasing attention in biomedical engineering. Current technology combines biocompatible materials with weaving processes to prepare leak-proof patches for tissue repair. The preparation methods often use polymer composite materials, while the weaving technology focuses on microstructure design to achieve efficient leak prevention. These technologies aim to improve the strength and bioactivity of the patch and promote the repair effect. Existing research focuses on material selection and structural optimization to enhance the overall performance of the patch.
[0003] Currently, biological leak-proof patches face the common problem of insufficient adhesion to wet tissue surfaces, making it difficult to achieve rapid and stable immediate sealing, which can easily lead to postoperative leakage risks. At the same time, the material has limited bioactivity and a weak ability to regulate excessive oxidative stress, which is not conducive to reducing inflammatory response and actively promoting tissue regeneration and integration, thus affecting the reliability of repair effects. Summary of the Invention
[0004] In order to overcome the shortcomings of the prior art, this invention provides a method for preparing and weaving a composite biological leak-proof patch with strong repair capabilities, which effectively solves the problems of postoperative leakage risk, obvious inflammatory response and insufficient tissue regeneration capacity faced by biological leak-proof patches on the market.
[0005] The technical solution adopted in this invention is as follows: This invention proposes a method for preparing and weaving a strong repair composite biological leak-proof patch, comprising the following raw materials in parts by weight: 30-50 parts of polyglycolic acid fiber; 20-40 parts of polyglycolic acid fiber; 10-30 parts of polydioxanone fiber; 5-15 parts of sodium carboxymethyl cellulose; 3-10 parts of chitosan; 2-8 parts of collagen; 0.1-2 parts of 1,3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride; and 1-5 parts of polyether ester catechol.
[0006] Furthermore, the preparation method of the polyether ester catechol includes the following steps:
[0007] S1. Under inert gas protection, a certain molar ratio of hydroxyl-terminated polyethylene glycol and lactide is placed in a reactor, and 0.1%-0.5% of stannous octoate as a catalyst is added. The ring-opening polymerization reaction is carried out at a specific temperature to obtain hydroxyl-terminated PEG-PLA diblock prepolymer.
[0008] S2. Dissolve the prepolymer obtained in step S1 in anhydrous dimethyl sulfoxide, cool to 4°C, add 3,4-dihydroxybenzoic acid and equimolar amounts of catalyst 4-dimethylaminopyridine and condensing agent N,N'-diisopropylcarbodiimide, and react at room temperature under light-protected conditions to esterify the carboxyl group of 3,4-dihydroxybenzoic acid with the terminal hydroxyl group of the prepolymer to obtain crude polyether ester catechol product;
[0009] S3. The reaction solution from step S2 is precipitated in ice-cold ether. The precipitate is collected and washed successively with dilute hydrochloric acid solution, sodium bicarbonate solution and deionized water until neutral. Finally, it is freeze-dried to obtain purified polyether ester catechol white solid.
[0010] Further, in step S1, the number average molecular weight of the hydroxyl-terminated polyethylene glycol is 1000-2000, and the molar ratio of the hydroxyl-terminated polyethylene glycol to lactide is 1:(8-12).
[0011] Furthermore, in step S1, the reaction temperature of the ring-opening polymerization reaction is 140-160℃, and the reaction time is 2-4 hours.
[0012] Furthermore, in step S2, the molar amount of 3,4-dihydroxybenzoic acid relative to the hydroxyl groups of the prepolymer is 3-6 times.
[0013] Furthermore, in step S2, the reaction is carried out for 18-24 hours under light-protected, room-temperature conditions.
[0014] Furthermore, the preparation method of the highly repairable composite biological leak-proof patch includes the following steps:
[0015] Polyglycolic acid, poly(ethylene glycol), and poly(p-dioxanone) fibers were three-dimensionally woven together in parts by weight to obtain a woven matrix. Carboxymethyl cellulose, chitosan, and collagen were dissolved and mixed separately, and then polyether ester catechol was added. The mixture environment was adjusted with MES buffer solution at pH 6.2, and EDC was added. The mixture was stirred evenly under light-proof and low-temperature conditions to form a composite coating solution. The woven matrix was immersed in the composite coating solution, and after vacuum degassing and centrifugation to remove excess liquid, it was freeze-dried. Then, it was chemically cross-linked with genipin solution, and then oxidatively activated with dilute sodium periodate solution. Finally, it was washed and dried to obtain the composite biological leak-proof patch.
[0016] Furthermore, the genipin crosslinking concentration is 0.5-1.5% (w / v), the crosslinking temperature is 2-6℃, and the time is 7-9 hours.
[0017] Furthermore, the oxidation activation treatment uses sodium periodate solution for 1-3 minutes.
[0018] Furthermore, the structural matrix is a three-layer sheet structure with a dense inner layer, a loose middle layer, and a medium-density outer layer; the specific parameters of the three-dimensional weaving are as follows: a vertical weaving machine with 48 spindles is used, the weaving angle is controlled at 40-50°, the inner layer adopts a satin weave with a porosity of 25-35%, the middle layer adopts a spaced weave with a porosity of 65-75%, the outer layer adopts a plain weave with a porosity of 45-55%, and the final patch thickness is 0.7-0.9 mm.
[0019] The beneficial effects achieved by the present invention using the above structure are as follows:
[0020] This solution proposes a method for preparing and weaving a highly repairable composite biological leak-proof patch. By utilizing the molecular structure of polyether ester catechol, the common problem of weak adhesion of biomaterials in body fluid environments can be effectively solved. The catechol functional groups in this molecule can mimic the action mechanism of natural mussel adhesion proteins, and under physiological conditions, they can interact strongly with various active groups on the tissue surface to form an instantaneous and stable interfacial bond. This characteristic enables the patch to quickly generate strong wet adhesion to the surrounding tissue after implantation, achieving immediate physical sealing, effectively preventing leakage of body fluids and blood, providing a stable and dry initial environment for the subsequent tissue repair process, and reducing the risk of postoperative complications.
[0021] The catechin groups in polyether ester catechins possess excellent antioxidant capabilities, which can neutralize excessive reactive oxygen free radicals at the wound site, thereby reducing oxidative stress and inflammatory responses in the early stages of implantation and creating a more favorable environment for cell migration and proliferation. In addition, studies have shown that the catechin structure has a positive promoting effect on the growth and migration of vascular endothelial cells. This, in synergy with the collagen contained in the patch, can accelerate the revascularization and granulation tissue formation at the damaged site, thus shifting from passive isolation to active guidance and improving the quality and speed of tissue repair. Attached Figure Description
[0022] Figure 1 The figure shows the wet adhesion test results of a composite biological leak-proof patch with strong repair proposed in this invention.
[0023] Figure 2 The figure shows the experimental results of the antioxidant and repair-promoting effects of a composite biological leak-proof patch with strong repair proposed in this invention.
[0024] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof. Detailed Implementation
[0025] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.
[0026] Example 1:
[0027] Preparation and Fabrication Method of a Highly Repairing Composite Bio-based Leak-proof Patch
[0028] Under inert gas protection, hydroxyl-terminated polyethylene glycol (PEG) and lactide (PEG) with a molar ratio of 1:8 were placed in a reactor, wherein the number average molecular weight of the hydroxyl-terminated PEG was 1000. Stannous octoate (0.5% by mass of total monomers) was added as a catalyst, and ring-opening polymerization was carried out at 140°C for 4 hours to obtain a hydroxyl-terminated PEG-PLA diblock prepolymer. The obtained prepolymer was dissolved in anhydrous dimethyl sulfoxide, cooled to 4°C, and 3,4-dihydroxybenzoic acid was added in a molar ratio relative to the hydroxyl groups of the prepolymer. Three times the amount of catalyst 4-dimethylaminopyridine and equimolar amounts of condensing agent N,N'-diisopropylcarbodiimide were reacted at room temperature for 18 hours under light-protected conditions to esterify the carboxyl group of 3,4-dihydroxybenzoic acid with the terminal hydroxyl group of the prepolymer, yielding crude polyether ester catechol. The reaction solution was precipitated in ice-cold diethyl ether, the precipitate was collected, and washed successively with dilute hydrochloric acid solution, sodium bicarbonate solution, and deionized water until neutral. Finally, it was freeze-dried to obtain purified polyether ester catechol as a white solid.
[0029] A woven matrix was obtained by three-dimensionally weaving 30 parts of polyglycolic acid, 20 parts of poly(ethylene lactide), and 10 parts of poly(p-dioxanone) fiber. 5 parts of carboxymethyl cellulose, 3 parts of chitosan, and 2 parts of collagen were dissolved and mixed separately, and then polyether ester catechol was added. The mixture was adjusted using MES buffer solution at pH 6.2, and 0.1 parts of 1,3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride were added. The mixture was stirred evenly under light-protected and low-temperature conditions to form a composite coating solution.
[0030] A woven substrate was prepared, which consisted of a three-layer sheet structure with a dense inner layer, a loose middle layer, and a medium-density outer layer. Specific parameters for the three-dimensional weaving were as follows: a vertical weaving machine with 48 spindles was used, the weaving angle was controlled at 40°, the inner layer used a satin weave with a porosity of 25%, the middle layer used a spaced weave with a porosity of 65%, and the outer layer used a plain weave with a porosity of 45%. The final patch thickness was 0.7 mm. The woven substrate was immersed in a composite coating liquid, and after vacuum degassing and centrifugation to remove excess liquid, it was freeze-dried. Subsequently, chemical crosslinking was performed using a genipin solution at a concentration of 0.5% (w / v) at a temperature of 2°C for 7 hours. Then, oxidation activation treatment was performed using a dilute sodium periodate solution for 1 minute. Finally, after washing and drying, the composite biological leak-proof patch was obtained.
[0031] Example 2:
[0032] Preparation and Fabrication Method of a Highly Repairing Composite Bio-based Leak-proof Patch
[0033] Under inert gas protection, hydroxyl-terminated polyethylene glycol (PEG) and lactide (PEG) with a molar ratio of 1:10 were placed in a reactor, wherein the number average molecular weight of the hydroxyl-terminated PEG was 1500. Stannous octoate (0.5% by mass of the total monomers) was added as a catalyst, and ring-opening polymerization was carried out at 150°C for 3 hours to obtain a hydroxyl-terminated PEG-PLA diblock prepolymer. The obtained prepolymer was dissolved in anhydrous dimethyl sulfoxide, cooled to 4°C, and 3,4-dihydroxybenzoic acid was added relative to the hydroxyl groups of the prepolymer. Four molar amounts of catalyst 4-dimethylaminopyridine and equimolar amounts of condensing agent N,N'-diisopropylcarbodiimide were reacted at room temperature for 21 hours under light-protected conditions to esterify the carboxyl group of 3,4-dihydroxybenzoic acid with the terminal hydroxyl group of the prepolymer, yielding crude polyether ester catechol. The reaction solution was precipitated in icy diethyl ether, the precipitate was collected, and washed successively with dilute hydrochloric acid solution, sodium bicarbonate solution, and deionized water until neutral. Finally, it was freeze-dried to obtain purified polyether ester catechol as a white solid.
[0034] A woven matrix was obtained by three-dimensionally weaving 40 parts of polyglycolic acid, 30 parts of poly(ethylene lactide), and 20 parts of poly(p-dioxanone) fiber. 10 parts of carboxymethyl cellulose, 6 parts of chitosan, and 5 parts of collagen were dissolved and mixed separately, and then 3 parts of polyether ester catechol were added. The mixture was adjusted with MES buffer at pH 6.2, and 1 part of 1,3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride was added. The mixture was stirred evenly under light-protected and low-temperature conditions to form a composite coating solution.
[0035] A woven substrate was prepared, which has a three-layer sheet structure with a dense inner layer, a loose middle layer, and a medium-density outer layer. The specific parameters of the three-dimensional weaving are as follows: a vertical weaving machine with 48 spindles is used, the weaving angle is controlled at 45°, the inner layer adopts a satin weave with a porosity of 30%, the middle layer adopts a spaced weave with a porosity of 70%, and the outer layer adopts a plain weave with a porosity of 50%. The final patch thickness is 0.8 mm. The woven substrate is immersed in a composite coating liquid, and after vacuum degassing and centrifugation to remove excess liquid, it is freeze-dried. Then, it is chemically crosslinked with genipin solution at a concentration of 1% (w / v) at a crosslinking temperature of 4°C for 8 hours. Then, it is oxidized and activated with dilute sodium periodate solution for 2 minutes. Finally, it is washed and dried to obtain the composite biological leak-proof patch.
[0036] Example 3:
[0037] Preparation and Fabrication Method of a Highly Repairing Composite Bio-based Leak-proof Patch
[0038] Under inert gas protection, hydroxyl-terminated polyethylene glycol (PEG) and lactide (PEG) with a molar ratio of 1:12 were placed in a reactor, wherein the number average molecular weight of the hydroxyl-terminated PEG was 2000. Stannous octoate (0.5% by mass of total monomers) was added as a catalyst, and ring-opening polymerization was carried out at 160°C for 2 hours to obtain a hydroxyl-terminated PEG-PLA diblock prepolymer. The obtained prepolymer was dissolved in anhydrous dimethyl sulfoxide, cooled to 4°C, and 3,4-dihydroxybenzoic acid was added relative to the hydroxyl groups of the prepolymer. Six molar amounts of catalyst 4-dimethylaminopyridine and equimolar amounts of condensing agent N,N'-diisopropylcarbodiimide were reacted at room temperature for 24 hours under light-protected conditions to esterify the carboxyl group of 3,4-dihydroxybenzoic acid with the terminal hydroxyl group of the prepolymer, yielding crude polyether ester catechol. The reaction solution was precipitated in icy diethyl ether, the precipitate was collected, and washed successively with dilute hydrochloric acid solution, sodium bicarbonate solution, and deionized water until neutral. Finally, it was freeze-dried to obtain purified polyether ester catechol as a white solid.
[0039] A woven matrix was obtained by three-dimensionally weaving 50 parts of polyglycolic acid, 40 parts of poly(ethylene lactide), and 30 parts of poly(p-dioxanone) fiber. 15 parts of carboxymethyl cellulose, 10 parts of chitosan, and 8 parts of collagen were dissolved and mixed separately, and then 5 parts of polyether ester catechol were added. The mixture was adjusted with MES buffer solution at pH 6.2, and 2 parts of 1,3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride were added. The mixture was stirred evenly under light-protected and low-temperature conditions to form a composite coating solution.
[0040] A woven substrate was prepared, which has a three-layer sheet structure with a dense inner layer, a loose middle layer, and a medium-density outer layer. The specific parameters of the three-dimensional weaving are as follows: a vertical weaving machine with 48 spindles is used, the weaving angle is controlled at 50°, the inner layer adopts a satin weave with a porosity of 35%, the middle layer adopts a spaced weave with a porosity of 75%, and the outer layer adopts a plain weave with a porosity of 55%. The final patch thickness is 0.9 mm. The woven substrate is immersed in a composite coating liquid, and after vacuum degassing and centrifugation to remove excess liquid, it is freeze-dried. Then, it is chemically crosslinked with genipin solution at a crosslinking concentration of 1.5% (w / v) at a crosslinking temperature of 6°C for 9 hours. Then, it is oxidized and activated with dilute sodium periodate solution for 3 minutes. Finally, it is washed and dried to obtain the composite biological leak-proof patch.
[0041] The results are as follows Figure 1 As shown, the interfacial bonding performance of the patch under simulated physiological conditions was evaluated using a wet adhesion test system. Tensile-shear strength tests showed that the experimental group patches could withstand significantly higher mechanical loads than the control group, and the values increased systematically with increasing polyether ester catechol content, with Example 3 exhibiting the highest load-bearing capacity. In the peel strength test, the experimental group patches demonstrated excellent peel resistance, with peel energy far superior to the control group, indicating a stronger and more durable bond between the patch and the tissue interface. Simultaneous leakage tests further verified the actual effect of the adhesion strength; the experimental group patches, especially in Example 3, achieved a complete seal for over 30 minutes, effectively resisting fluid leakage. Overall, the experimental results fully demonstrate that this composite patch can achieve immediate and reliable physical sealing through strong wet adhesion, providing crucial technical support for postoperative leakage prevention and highlighting the significant contribution of polyether ester catechol in optimizing patch function.
[0042] The results are as follows Figure 2 As shown, in vitro antioxidant experiments demonstrated that the patch exhibited significant free radical scavenging ability and effectively reduced intracellular reactive oxygen species levels, reflecting its positive effect in alleviating oxidative stress. Cell migration and proliferation experiments showed that the patch significantly promoted endothelial cell migration and proliferation, demonstrating its ability to stimulate cell activity. Angiogenesis experiments showed that the patch effectively increased the formation of tubular structures, demonstrating its excellent effect in promoting angiogenesis. In vivo animal model experiments showed that the patch significantly increased tissue microvascular density and cell proliferation index, while significantly reducing the expression of inflammatory factors and oxidative damage indicators, demonstrating its comprehensive efficacy in promoting tissue repair and regeneration and effectively controlling inflammatory responses.
[0043] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.
[0044] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.
[0045] The present invention and its embodiments have been described above. This description is not restrictive, and the accompanying drawings are only one embodiment of the present invention; the actual structure is not limited thereto. In conclusion, if those skilled in the art are inspired by this description and design similar structures and embodiments without departing from the spirit of the invention, such designs should fall within the protection scope of the present invention.
Claims
1. A composite biological leak-proof patch with strong repair properties, characterized in that: The raw materials include the following parts by weight: 30-50 parts of polyglycolic acid fiber; 20-40 parts of polyglycolic acid fiber; 10-30 parts of polydioxanone fiber; 5-15 parts of sodium carboxymethyl cellulose; 3-10 parts of chitosan; 2-8 parts of collagen; 0.1-2 parts of 1,3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride; and 1-5 parts of polyether ester catechol.
2. The composite biological leak-proof patch with strong repair capability according to claim 1, characterized in that, The preparation method of the polyether ester catechin includes the following steps: S1. Under inert gas protection, a certain molar ratio of hydroxyl-terminated polyethylene glycol and lactide is placed in a reactor, and 0.1%-0.5% of stannous octoate as a catalyst is added. The ring-opening polymerization reaction is carried out at a specific temperature to obtain hydroxyl-terminated PEG-PLA diblock prepolymer. S2. Dissolve the prepolymer obtained in step S1 in anhydrous dimethyl sulfoxide, cool to 4°C, add 3,4-dihydroxybenzoic acid and equimolar amounts of catalyst 4-dimethylaminopyridine and condensing agent N,N'-diisopropylcarbodiimide, and react at room temperature under light-protected conditions to esterify the carboxyl group of 3,4-dihydroxybenzoic acid with the terminal hydroxyl group of the prepolymer to obtain crude polyether ester catechol product; S3. The reaction solution from step S2 is precipitated in ice-cold ether. The precipitate is collected and washed successively with dilute hydrochloric acid solution, sodium bicarbonate solution and deionized water until neutral. Finally, it is freeze-dried to obtain purified polyether ester catechol white solid.
3. The composite biological leak-proof patch with strong repair capability according to claim 2, characterized in that: In step S1, the number average molecular weight of the hydroxyl-terminated polyethylene glycol is 1000-2000, and the molar ratio of the hydroxyl-terminated polyethylene glycol to lactide is 1:(8-12).
4. The composite biological leak-proof patch with strong repair capability according to claim 3, characterized in that: In step S1, the reaction temperature of the ring-opening polymerization reaction is 140-160℃, and the reaction time is 2-4 hours.
5. The composite biological leak-proof patch with strong repair capability according to claim 4, characterized in that: In step S2, the molar amount of 3,4-dihydroxybenzoic acid relative to the hydroxyl groups of the prepolymer is 3-6 times.
6. The composite biological leak-proof patch with strong repair according to claim 5, characterized in that: In step S2, the reaction is carried out for 18-24 hours under light-protected, room temperature conditions.
7. A method for preparing a highly repairable composite biological leak-proof patch according to any one of claims 1-6, characterized in that, The preparation method of the highly repairable composite biological leak-proof patch includes the following steps: Polyglycolic acid, poly(ethylene glycol), and poly(p-dioxanone) fibers were three-dimensionally woven together in parts by weight to obtain a woven matrix. Carboxymethyl cellulose, chitosan, and collagen were dissolved and mixed separately, and then polyether ester catechol was added. The mixture environment was adjusted with MES buffer solution at pH 6.2, and EDC was added. The mixture was stirred evenly under light-proof and low-temperature conditions to form a composite coating solution. The woven matrix was immersed in the composite coating solution, and after vacuum degassing and centrifugation to remove excess liquid, it was freeze-dried. Then, it was chemically cross-linked with genipin solution, and then oxidatively activated with dilute sodium periodate solution. Finally, it was washed and dried to obtain the composite biological leak-proof patch.
8. The method for preparing a highly repairable composite biological leak-proof patch according to claim 7, characterized in that: The genipin crosslinking concentration is 0.5-1.5% (w / v), the crosslinking temperature is 2-6℃, and the time is 7-9 hours.
9. The method for preparing a highly repairable composite biological leak-proof patch according to claim 8, characterized in that: The oxidation activation treatment uses sodium periodate solution and the treatment time is 1-3 minutes.
10. A method for fabricating a highly repairable composite biological leak-proof patch according to any one of claims 1-9, characterized in that: The structural substrate is a three-layer sheet structure with a dense inner layer, a loose middle layer, and a medium-density outer layer. The specific parameters of the three-dimensional weaving are as follows: a vertical weaving machine with 48 spindles is used, the weaving angle is controlled at 40-50°, the inner layer adopts a satin weave with a porosity of 25-35%, the middle layer adopts a spaced weave with a porosity of 65-75%, the outer layer adopts a plain weave with a porosity of 45-55%, and the final patch thickness is 0.7-0.9 mm.